Phosphorylation of Serine 2 within the RNA Polymerase II C-Terminal Domain Couples Transcription and 3′ End Processing

Ahn, Shihyun; Kim, Minkyu; Buratowski, Stephen

doi:10.1016/s1097-2765(03)00492-1

Cited by 454 publications

(476 citation statements)

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“…Ser2 phosphorylated CTD helps to recruit and/or stabilize polyadenylation factors, thereby facilitating coupling of transcription and mRNA 39-end formation. For instance, in yeast, Ser2 phosphorylation of the CTD potentiates interaction with the essential polyadenylation factor Pcf11 (de Vries et al 2000;Barilla et al 2001;Licatalosi et al 2002;Ahn et al 2004). The H3-K36 methyltransferase Set2 binds elongating RNAPII, recognizing the doubly phosphorylated CTD (Ser5/Ser2) (Hampsey and Reinberg 2003;Kizer et al 2005).…”

Section: Ctd Of the Rnapii Large Subunitmentioning

confidence: 99%

“…In yeast, mutations and conditional depletion of factors involved in pre-mRNA cleavage and polyadenylation, including homologs of CstF-64 (Rna15), CstF-77 (Rna14), Pcf11, CPSF160 (Yhh1), CPSF-73 (Ysh1), and Ssu72, result in read-through at the 39-end of protein-coding genes (Birse et al 1998;Dichtl et al 2002;Steinmetz and Brow 2003;Garas et al 2008). Accordingly, ChIP assays suggest that 39-end processing factors, including Pcf11, Rna14, and Rna15, become associated with the RNAPII EC at the poly(A) site, in a Ser2 phosphorylated CTD-dependant manner (Ahn et al 2004;Kim et al 2004a;Luo et al 2006). Other components of the yeast polyadenylation machinery, including homologs of CPSF-100, CPSF-30, and symplekin, are also associated with the 39-ends of protein-coding genes (Kim et al 2004a).…”

Section: Trans-acting Factor Dynamics At the Poly(a) Site Affect Tranmentioning

confidence: 99%

“…In ChIP experiments, factors such as the Paf1C and the TREX/THO complex, which functions in mRNP biogenesis and maintenance of genome integrity (Garcia-Rubio et al 2008), cross-link throughout genes, but their levels are reduced on passage through the poly(A) site, suggesting they are released from the EC (Ahn et al 2004;Kim et al 2004a). Dissociation of a CstF64-interacting protein, the transcriptional coactivator PC4 (human homolog of Sub1), at the poly(A) site renders RNAPII competent for termination, and genetic evidence in yeast suggests that Sub1/PC4 has an evolutionarily conserved anti-terminator activity (Calvo and Manley 2001).…”

Section: Trans-acting Factor Dynamics At the Poly(a) Site Affect Tranmentioning

confidence: 99%

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Transcription termination by nuclear RNA polymerases

Richard

Manley²

2009

Genes Dev.

291

326

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Gene transcription in the cell nucleus is a complex and highly regulated process. Transcription in eukaryotes requires three distinct RNA polymerases, each of which employs its own mechanisms for initiation, elongation, and termination. Termination mechanisms vary considerably, ranging from relatively simple to exceptionally complex. In this review, we describe the present state of knowledge on how each of the three RNA polymerases terminates and how mechanisms are conserved, or vary, from yeast to human.

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Section: Ctd Of the Rnapii Large Subunitmentioning

confidence: 99%

Section: Trans-acting Factor Dynamics At the Poly(a) Site Affect Tranmentioning

confidence: 99%

Section: Trans-acting Factor Dynamics At the Poly(a) Site Affect Tranmentioning

confidence: 99%

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Transcription termination by nuclear RNA polymerases

Richard

Manley²

2009

Genes Dev.

291

326

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“…However, the potential role of the pol II CTD and CTD phosphorylation in this process remains unclear. Recruitment of the TREX complex to transcribed genes is not dependent on the S2 kinase, Ctk1 in yeast (Ahn et al, 2004), and the association of the human TREX complex to mRNA might be coupled to transcription indirectly through splicing (Masuda et al, 2005). On the other hand, interestingly, Jones and colleagues show that mammalian Spt6 that selectively associates S2-phosphorylated CTD concomitantly recruits REF/Aly and UAP56 via Iws1 (Yoh et al, 2007), suggesting an alternative mechanism of cotranscriptional coupling of mRNA export in mammalian system independently of THO or splicing, but depends on CTD phosphorylation.…”

Section: Deciphering the Ctd Codementioning

confidence: 99%

“…Like capping, pol II CTD can play an important role in splicing by regulating the efficiency and specificity of splicing as well as recruiting the machinery. However, the functional specificity of the two different serines is unknown.Similar to splicing, the 3'-end processing of mRNA is affected in cells through a deletion of the pol II CTD or a loss of CTD phosphorylation, even though nascent RNA carries the consensus recognition sites (Fong and Bentley, 2001;Proudfoot et al, 2002;Skaar and Greenleaf, 2002;Ahn et al, 2004). 3'-end modifications of the pre-mRNA proceeds through two steps; endonucleolytic cleavage of the 250 Exp.…”

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confidence: 99%

RNA polymerase II carboxy-terminal domain with multiple connections

Cho¹

2007

Exp Mol Med

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The largest subunit of eukaryotic RNA polymerase II contains a unique domain at its carboxy-terminus, which is referred to as the carboxy-terminal domain (CTD). The CTD is made up of an evolutionarily conserved heptapeptide repeat (YSPTSPS). Over the past decade, there has been increasing attention on the role of the CTD in transcription regulation in the view of mRNA processing and chromatin remodeling. This paper provides a brief overview of the recent progress in the dynamic changes in CTD phosphorylation and its role in integrating multiple nuclear events.Keywords: carboxy-terminal domain kinase; chromatin; phosphorylation; histones; RNA polymerase II; RNA processing, post-transcriptional IntroductionThe largest subunit of eukaryotic RNA polymerase II (pol II) carboxy-terminal domain (CTD) consists of conserved heptapeptide repeats (Y 1 S 2 P 3 T 4 S 5 P 6 S 7 ) (Dahmus, 1996). Mammalian pol II CTD contains 52 repeats, whereas the yeast Saccharomyces cerevisiae CTD has 26-27. A deletion of the mouse, Drosophila, or yeast CTD is lethal. Therefore, the CTD is essential for the viability of an organism, even though the number of repeats can be reduced.Partial deletions of the CTD result in reduced transcription in vivo, and defective responses to various activators. The CTD acts as a platform to couple the mRNA metabolism and chromatin function to the transcription as it recruits various RNA processing/export and histone modifying factors to the transcription complex (Bentley, 2005;Buratowski, 2005;Phatnani and Greenleaf, 2006). This means that the CTD is very important for organizing various nuclear functions to acquire the proper regulation of gene expression. Those functions often depend on the CTD modification such as phosphorylation. Indeed, the CTD is rich in phosphoacceptor amino acid residues and undergoes reversible phosphorylation during the transcription cycle. Two forms of RNA pol II, which differ in the level of phosphorylation of the CTD, can be distinguished and are believed to have distinct functions in the transcription cycle; RNA pol IIa, with a hypophosphorylated CTD, is the form that assembles into the transcription initiation complexes, whereas pol IIo, with a hyperphosphorylated CTD is associated with the transcription elongation complexes. Phosphorylation occurs mainly at discrete serines (S) within the CTD repeats (S2, S5), which is then recognized by different proteins that interconnect the transcription to various nuclear metabolisms. Accordingly, serine phosphorylation is known as the 'CTD code', in a similar way that the 'histone code' refers to the histone modification (Buratowski, 2003). CTD with the phosphorylation codeEarlier models based on a two-step transcription cycle, in which pol IIa was assembled at the promoter and pol IIo carried out transcription elongation, have evolved to one with a more complex CTD phosphorylation cycle. Different modified forms of pol II dominate different stages of transcription (Komarnisky et al., 2000). Pol II assembled at the promoter is...

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mRNA Formation: 3′‐End

Wahle

Kühn

2021

Encyclopedia of Life Sciences

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Eukaryotic mRNAs are derived from precursors synthesised by RNA polymerase II. For 3′‐end formation, precursors are cleaved by an endonuclease, and a poly(A) tail is added. This processing reaction depends on signals in the pre‐mRNA, among them the ‘polyadenylation signal’ AAUAAA. Cleavage and polyadenylation are carried out by a multiprotein complex comprising, in yeast, a minimum of 13 polypeptides, many of which recognise RNA sequence motifs around the polyadenylation site. 3′‐end processing is coupled to transcription. Alternative polyadenylation, that is cleavage and polyadenylation of a precursor RNA at any of several sites, is widespread. The choice of polyadenylation site can affect the coding sequence or, more often, 3′‐UTR length. In the latter case, stability, translational efficiency or localisation of the RNA may be affected. Histone mRNAs are an exception: Their precursors are cleaved by a partially different set of factors, and no poly(A) tail is added. Key Concepts The 3′‐ends of eukaryotic mRNAs are generated by processing of the primary transcript, not by transcription termination. 3′‐end processing is essential for the production of mRNAs. 3′‐end processing takes place in the cell nucleus and consists of cleavage of the primary transcript followed by addition of a poly(A) tail to the upstream cleavage product. The machinery for 3′‐end processing is complex, comprising at least 13 polypeptides. 3′‐end processing occurs cotranscriptionally and is coupled to transcription and splicing. Alternative polyadenylation, that is the choice of different sites for cleavage and polyadenylation, can change the protein sequence encoded by the resulting mRNAs and/or mRNA regulation. Histone mRNAs in metazoans are the only known RNAs that are not polyadenylated; their 3′‐ends are generated by a simple cleavage reaction.

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Phosphorylation of Serine 2 within the RNA Polymerase II C-Terminal Domain Couples Transcription and 3′ End Processing

Cited by 454 publications

References 55 publications

Transcription termination by nuclear RNA polymerases

Transcription termination by nuclear RNA polymerases

RNA polymerase II carboxy-terminal domain with multiple connections

mRNA Formation: 3′‐End

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